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Fault slip is a complex natural phenomenon involving multiple spatiotemporal scales from seconds to days to weeks. To understand the physical and chemical processes responsible for the full fault slip spectrum, a multidisciplinary approach is highly recommended. The Near Fault Observatories (NFOs) aim at providing high-precision and spatiotemporally dense multidisciplinary near-fault data, enabling the generation of new original observations and innovative scientific products. The Alto Tiberina Near Fault Observatory is a permanent monitoring infrastructure established around the Alto Tiberina fault (ATF), a 60 km long low-angle normal fault (mean dip 20°), located along a sector of the Northern Apennines (central Italy) undergoing an extension at a rate of about 3 mm yr−1. The presence of repeating earthquakes on the ATF and a steep gradient in crustal velocities measured across the ATF by GNSS stations suggest large and deep (5–12 km) portions of the ATF undergoing aseismic creep. Both laboratory and theoretical studies indicate that any given patch of a fault can creep, nucleate slow earthquakes, and host large earthquakes, as also documented in nature for certain ruptures (e.g., Iquique in 2014, Tōhoku in 2011, and Parkfield in 2004). Nonetheless, how a fault patch switches from one mode of slip to another, as well as the interaction between creep, slow slip, and regular earthquakes, is still poorly documented by near-field observation. With the strainmeter array along the Alto Tiberina fault system (STAR) project, we build a series of six geophysical observatory sites consisting of 80–160 m deep vertical boreholes instrumented with strainmeters and seismometers as well as meteorological and GNSS antennas and additional seismometers at the surface. By covering the portions of the ATF that exhibits repeated earthquakes at shallow depth (above 4 km) with these new observatory sites, we aim to collect unique open-access data to answer fundamental questions about the relationship between creep, slow slip, dynamic earthquake rupture, and tectonic faulting.

The general basin and range Apennine topographic characteristic is generally attributed to the presently active normal fault systems, whose long-term activity (throughout the Quaternary) is supposed to have been responsible for the creation of morphological/structural highs and lows. By coupling field geological survey and geophysical investigations, we reconstructed the 3-D geological model of an inner tectonic basin of the central Apennines, the Subequana Valley, bounded to the northeast by the southern segment of one of the major active and seismogenic normal faults of the Apennines, known as the Middle Aterno Valley–Subequana Valley fault system. Our analyses revealed that, since the late Pliocene, the basin evolved in a double half-graben configuration through a polyphase tectonic development. An early phase, Late Pliocene–Early Pleistocene in age, was controlled by the ENE–WSW-striking and SSE-dipping Avezzano–Bussi fault, that determined the formation of an early depocentre towards the N–NW. Subsequently, the main fault became the NW–SE-striking faults, which drove the formation during the Quaternary of a new fault-related depocentre towards the NE. By considering the available geological information, a similar structural evolution has likely involved three close tectonic basins aligned along the Avezzano–Bussi fault, namely the Fucino Basin, the Subequana Valley, and the Sulmona Basin, and it has been probably experienced by other tectonic basins of the chain. The present work therefore points out the role of pre-existing transverse tectonic structures, inherited by previous tectonic phases, in accommodating the ongoing tectonic deformation and, consequently, in influencing the structural characteristics of the major active normal faults. This has implications in terms of earthquake fault rupture propagation and segmentation. Lastly, the morpho-tectonic setting of the Apennine chain results from the superposition of deformation events whose geological legacy must be considered in a wider evolutionary perspective. Our results testify that a large-scale basin and range geomorphological feature – often adopted for morpho-tectonic and kinematic evaluations in active extensional contexts, as in the Apennines – just led by range-bounding active normal faults may be actually simplistic, as it could not be applied everywhere, owing to peculiar complexities of the local tectonic histories.

In October and November 2002, the Molise region (southern Italy) was struck by two moderate magnitude earthquakes within 24 hours followed by an one month long aftershocks sequence. Soon after the first mainshock (October 31st, 10.32 UTC, Mw 5.7), we deployed a temporary network of 35 three-component seismic stations. At the time of occurrence of the second main event (November 1st, 15.08 UTC, Mw 5.7) the eight local stations already installed allowed us to well constrain the hypocentral parameters. We present the location of the two mainshocks and 1929 aftershocks with 2 < ML < 4.2. Earthquake distribution reveals a E-trending 15 km long fault system composed by two main segments ruptured by the two mainshocks. Aftershocks define two sub-vertical dextral strike-slip fault segments in agreement with the mainshock fault plane solutions. P- and T-axes retrieved from 170 aftershocks focal mechanisms show a coherent kinematics: with a sub-horizontal NW and NE-trending P and T-axes, respectively. For a small percentage of focal mechanisms (∼ 10%) a rotation of T axes is observed, resulting in thrust solutions. The Apenninic active normal fault belt is located about 80 km westward of the 2002 epicentral area and significant seismicity occurs only 20-50 km to the east, in the Gargano promontory. Seismic hazard was thought to be small for this region because neither historical earthquake are reported in the Italian seismic catalogue or active faults were previously identified. In this context, the 2002 seismic sequence highlights the existence of trans-pressional active tectonics in between the extensional Apenninic belt and the Apulian foreland. [ABSTRACT FROM AUTHOR]

Substituted benzaldehydes are the most commonly used natural-occurring flavours in the world. The consumer's preference for 'natural or organic' aromas has increased the request for flavours possessing the 'natural' status. The resulting shortage of aromatic aldehydes of extractive origin, such as vanillin, veratraldehyde and piperonal, can be offset by developing a new biotechnological synthesis method. Here, we report a study on the microbiological reduction of five natural benzoic acid derivatives, namely p-anisic, vanillic, veratric, piperonylic and eudesmic acids, to produce the corresponding fragrant aldehydes. We found that different Basidiomycota strains can efficiently perform this transformation, with good chemical selectivity and tolerance to the toxicity of substrates and products. Besides confirming the carboxylic acid reductase activity of the already studied fungi Pycnoporus cinnabarinus, we discovered that other species such as Pleurotus eryngii, Pleurotus sapidus and Laetiporus sulphureus as well as the non-ligninolytic fungi Lepista nuda are valuable microorganisms for the synthesis of anisaldehyde, vanillin, veratraldehyde, piperonal and 3,4,5-trimethoxybenzaldehyde from the corresponding acids. According to our findings, we propose a reliable process for the preparation of the above-mentioned aldehydes, in natural form. KEY POINTS: • Fragrant benzaldehydes were obtained by biotransformation. • Basidiomycota strains reduced substituted benzoic acid to the corresponding aldehydes. • Anisaldehyde, vanillin, veratraldehyde, piperonal and 3,4,5-trimethoxybenzaldehyde were prepared in natural form., (© 2024. The Author(s).)

Introduction: The skin is often exposed to harmful stimuli that might compromise its integrity and functionality. After an injury, the skin has a limited capability to restore its complex structure, and in the case of severe skin damage, surgical operations and rapid application of wound dressings are often required to promote optimal wound healing. Nowadays, collagen-based biomaterials are widely used in combination with bioactive molecules able to prevent excessive inflammation and possible infections. In line with a circular economy and blue biotechnology approach, it was recently demonstrated that both collagen and bioactive molecules (i.e., antioxidant compounds) can be sustainably obtained from sea food by-products and effectively used for biomaterial development. Herein, we describe and compare the application of two marine collagen-based wound dressings (CBWDs), produced with materials obtained from sea urchin food waste, for the treatment of skin lesions in a wound healing organ culture (WHOC) model., Methods: The ex vivo WHOC model was set up starting from rat skin explants and the induced lesions were assigned into three different groups: control (CTRL) group, not treated, marine collagen wound dressing (MCWD) group, and antioxidants-enriched marine collagen wound dressing (A-MCWD) group. After 5 and 10 days, specimens were examined for organ maintenance and assessed for the healing process., Results: Immunohistochemical results showed that both CBWDs were similarly successful in prolonging skin repair, preserving the epidermal barrier up to 5 days under static culture conditions. Histological and gene expression analysis highlighted that the A-MCWD might support and accelerate skin wound healing by exerting antioxidant activity and counteracting inflammation., Discussion: Overall, these findings underline the potential of sea urchin food waste as a novel resource for the development of functional medical devices for the treatment of skin wounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zivelonghi, Melotti, Carolo, Venerando, Roncoroni, Martinelli, Maccatrozzo, Marzorati, Sugni and Patruno.)

Serenoa repens is a medicinal plant well-known for its therapeutic potential in treating various urological disorders and prevention of prostatic cancer. However, the extraction process in the pharmaceutical industry leads to the generation of plant residues, typically discarded, wasting valuable resources. In this study, we aimed to explore a series of green extraction strategies to effectively valorize the residues of Serenoa repens fruits. Initially, we employed supercritical CO 2 (1.2% yield on dry biomass) on the discarded biomass to identify and quantify residual fatty acids and polyprenols (1.6% of the extract dry weight), a class of unsaturated isoprenoid alcohols with promising biomedical applications. Subsequently, subcritical water extraction was utilized on the exhausted biomass to extract polar compounds. An increase in the extraction yield was observed with the rise in processing temperature up to 180 °C (yields were found higher than 26%). Phenolic compounds and carbohydrate macromolecules profiles were affected by the increased hydrolytic conditions. Polar extracts exhibited robust bioactivities, demonstrating significant antioxidant activity and antimicrobial efficacy against Gram-positive and Gram-negative bacteria strains. Extracts obtained at 180 °C demonstrated the highest efficacy. Furthermore, in vitro assessment of mannans-rich fraction provided a new perspective of potential applications in the cosmeceuticals field. Results underscore the potential of the sustainable extraction biorefinery for the residue of this medicinal plant and demonstrate that, harnessing these bioactive compounds, new sustainable and eco-friendly approaches for its complete utilization can be offered, thereby promoting near-zero waste practices and contributing to a more sustainable future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Obesity is a global epidemic that affects millions worldwide and can be a deterrent to surgical procedures in the population waiting for kidney transplantation. However, the literature on the topic is controversial. This study evaluates the impact of body mass index (BMI) on complications after renal transplantation, and identifies factors associated with major complications to develop a prognostic risk score., Methods: A correlation analysis between BMI and early and late complications was first performed, followed by a univariate and multivariate logistic regression analysis. The 302 included patients were divided into obese (BMI ≥ 30 kg/m 2 ) and non-obese (BMI ≤ 30 kg/m 2 ) groups. Correlation analysis showed that delayed graft function (DGF) was the only obesity-associated complication ( p = 0.044). Logistic regression analysis identified female sex, age ≥ 57 years, BMI ≥ 25 and ≥30 kg/m 2 , previous abdominal and/or urinary system surgery, and Charlson morbidity Score ≥ 3 as risk factors for significant complications. Based on the analyzed data, we developed a nomogram and a prognostic risk score., Results: The model's area (AUC) was 0.6457 (95% IC: 0.57; 0.72). The percentage of cases correctly identified by this model retrospectively applied to the entire cohort was 73.61%., Conclusions: A high BMI seems to be associated with an increased risk of DGF, but it does not appear to be a risk factor for other complications. Using an easy-to-use model, identification, and stratification of individualized risk factors could help to identify the need for interventions and, thus, improve patient eligibility and transplant outcomes. This could also contribute to maintaining an approach with high ethical standards.

Approximately 75,000 tons of different sea urchin species are globally harvested for their edible gonads. Applying a circular economy approach, we have recently demonstrated that non-edible parts of the Mediterranean Sea urchin Paracentrotus lividus can be fully valorized into high-value products: antioxidant pigments (polyhydroxynaphthoquinones-PHNQs) and fibrillar collagen can be extracted to produce innovative biomaterials for biomedical applications. Can waste from other edible sea urchin species (e.g., Sphaerechinus granularis ) be similarly valorised? A comparative study on PHNQs and collagen extraction was conducted. PHNQ extraction yields were compared, pigments were quantified and identified, and antioxidant activities were assessed (by ABTS assay) and correlated to specific PHNQ presence (i.e., spinochrome E). Similarly, collagen extraction yields were evaluated, and the resulting collagen-based biomaterials were compared in terms of their ultrastructure, degradation kinetics, and resistance to compression. Results showed a partially similar PHNQ profile in both species, with significantly higher yield in P. lividus , while S. granularis exhibited better antioxidant activity. P. lividus samples showed higher collagen extraction yield, but S. granularis scaffolds showed higher stability. In conclusion, waste from different species can be successfully valorised through PHNQ and collagen extraction, offering diverse applications in the biomedical field, according to specific technical requirements.

This article describes a dataset of acceleration signals acquired from a low-cost Wireless Sensor Network (WSN) during seismic events that occurred in Central Italy. The WSN consists of 5 low-cost sensor nodes, each embedding an ADXL355 tri-axial MEMS accelerometer with a fixed sampling frequency of 250 Hz. The data was acquired from February 2023 to the end of June 2023. During this period, several earthquake sequences affected the area where the sensor network was installed. Continuous data was acquired from the WSN and then trimmed around the origin time of seismic events that occurred near the installation site, close to the city of Pollenza (MC), Italy. A total of 67 events were selected, whose data is available at the Istituto Nazionale di Geofisica e Vulcanologia (INGV) Seismology data center. The traces acquired from the WSN were then manually annotated by analysts from INGV. Annotations include picking time for P and S phases, when distinguishable from the background noise, alongside an associated uncertainty level for the manual annotations. The resulting dataset consists of 328 3 × 25,001 arrays, each associated with its metadata. The metadata includes event data (hypocenter position, origin time, magnitude, magnitude type, etc.), trace-related data (mean, median, maximum, and minimum amplitudes, manual picks, and picks uncertainty), and sensor-specific data (sensor name, sensitivity, and orientation). Furthermore, a small dataset consisting of non-seismic traces is included, with the goal of providing records of noise-only traces, relative to both electronic and environmental/anthropic noise sources. The dataset holds potential for training and developing Machine Learning or signal processing algorithms for seismic data with low signal-to-noise ratios. Additionally, it is valuable for research about earthquakes, structural health monitoring, and MEMS accelerometer performance in civil and seismic engineering applications., (© 2024 Published by Elsevier Inc.)

In this review, we focused on recent efforts in the design and development of materials with biomimetic properties. Innovative methods promise to emulate cell microenvironments and tissue functions, but many aspects regarding cellular communication, motility, and responsiveness remain to be explained. We photographed the state-of-the-art advancements in biomimetics, and discussed the complexity of a "bottom-up" artificial construction of living systems, with particular highlights on hydrogels, collagen-based composites, surface modifications, and three-dimensional (3D) bioprinting applications. Fast-paced 3D printing and artificial intelligence, nevertheless, collide with reality: How difficult can it be to build reproducible biomimetic materials at a real scale in line with the complexity of living systems? Nowadays, science is in urgent need of bioengineering technologies for the practical use of bioinspired and biomimetics for medicine and clinics.

An effective earthquake early warning system requires rapid and reliable earthquake source detection. Despite the numerous proposed epicenter localization solutions in recent years, their utilization within the Internet of Things (IoT) framework and integration with IoT-oriented cloud platforms remain underexplored. This paper proposes a complete IoT architecture for earthquake detection, localization, and event notification. The architecture, which has been designed, deployed, and tested on a standard cloud platform, introduces an innovative approach by implementing P-wave "picking" directly on IoT devices, deviating from traditional regional earthquake early warning (EEW) approaches. Pick association, source localization, event declaration, and user notification functionalities are also deployed on the cloud. The cloud integration simplifies the integration of other services in the architecture, such as data storage and device management. Moreover, a localization algorithm based on the hyperbola method is proposed, but here, the time difference of arrival multilateration is applied that is often used in wireless sensor network applications. The results show that the proposed end-to-end architecture is able to provide a quick estimate of the earthquake epicenter location with acceptable errors for an EEW system scenario. Rigorous testing against the standard of reference in Italy for regional EEW showed an overall 3.39 s gain in the system localization speed, thus offering a tangible metric of the efficiency and potential proposed system as an EEW solution.

The mutable collagenous tissue (MCT) of echinoderms possesses biological peculiarities that facilitate native collagen extraction and employment for biomedical applications such as regenerative purposes for the treatment of skin wounds. Strategies for skin regeneration have been developed and dermal substitutes have been used to cover the lesion to facilitate cell proliferation, although very little is known about the application of novel matrix obtained from marine collagen. From food waste we isolated eco-friendly collagen, naturally enriched with glycosaminoglycans, to produce an innovative marine-derived biomaterial assembled as a novel bi-layered skin substitute (Marine Collagen Dermal Template or MCDT). The present work carried out a preliminary experimental in vivo comparative analysis between the MCDT and Integra, one of the most widely used dermal templates for wound management, in a rat model of full-thickness skin wounds. Clinical, histological, and molecular evaluations showed that the MCDT might be a valuable tool in promoting and supporting skin wound healing: it is biocompatible, as no adverse reactions were observed, along with stimulating angiogenesis and the deposition of mature collagen. Therefore, the two dermal templates used in this study displayed similar biocompatibility and outcome with focus on full-thickness skin wounds, although a peculiar cellular behavior involving the angiogenesis process was observed for the MCDT.

Background & Aims: Cholangiocarcinoma (CCA) is a primary liver tumour characterised by a poor prognosis and limited therapeutic options. Available 3D human CCA models fail to faithfully recapitulate the tumour niche. We aimed to develop an innovative patient-specific CCA-on-chip platform., Methods: A CCA tumour microenvironment was recapitulated on a microfluidic three-channel chip using primary CCA cells, cancer-associated fibroblasts (CAFs), endothelial cells, and T cells isolated from CCA specimens (n = 6). CAF and CCA cells were co-cultured in the central channel, flanked by endothelial cells in one lateral channel, recreating a tubular structure. An extensive characterisation of this platform was carried out to investigate its diffusion ability, hydrogel properties, and changes in matrix composition. Cell phenotype and functional properties were assessed., Results: Primary cells seeded on the microfluidic device were shown to reproduce the architectural structure and maintain the original phenotype and functional properties. The tumour niche underwent a deep remodelling in the 3D device, with an increase in hydrogel stiffness and extracellular matrix deposition, mimicking in vivo CCA characteristics. T cells were incorporated into the device to assess its reliability for immune cell interaction studies. Higher T cell migration was observed using cells from patients with highly infiltrated tumours. Finally, the drug trial showed the ability of the device to recapitulate different drug responses based on patient characteristics., Conclusions: We presented a 3D CCA platform that integrates the major non-immune components of the tumour microenvironment and the T cell infiltrate, reflecting the CCA niche. This CCA-on-chip represents a reliable patient-specific 3D platform that will be of help to further elucidate the biological mechanisms involved in CCA and provide an efficient tool for personalised drug testing., Impact and Implications: An innovative patient-specific cholangiocarcinoma (CCA)-on-chip platform was successfully developed, integrating the major components of the tumour microenvironment (tumour cells, cancer-associated fibroblasts, endothelial cells, and immune infiltrate) and faithfully mimicking the CCA niche. This CCA-on-chip represents a powerful tool for unravelling disease-associated cellular mechanisms in CCA and provides an efficient tool for personalised drug testing., Competing Interests: AL reports receiving consulting fees from Advanz Pharma, AlfaSigma, Takeda, and Albireo Pharma, and speaker fees from Gilead, AbbVie, MSD, Intercept Pharma, AlfaSigma, GSK, and Incyte. All other authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Coping with a zero-waste, more sustainable economy represents the biggest challenge for food market nowadays. We have previously demonstrated that by applying smart multidisciplinary waste management strategies to purple sea urchin ( Paracentrotus lividus ) food waste, it is possible to obtain both a high biocompatible collagen to produce novel skin substitutes and potent antioxidant pigments, namely polyhydroxynapthoquinones (PHNQs). Herein, we have analyzed the biological activities of the PHNQs extract, composed of Spinochrome A and B, on human skin fibroblast cells to explore their future applicability in the treatment of non-healing skin wounds with the objective of overcoming the excessive oxidative stress that hinders wound tissue regeneration. Our results clearly demonstrate that the antioxidant activity of PHNQs is not restricted to their ability to scavenge reactive oxygen species; rather, it can be traced back to an upregulating effect on the expression of superoxide dismutase 1, one of the major components of the endogenous antioxidant enzymes defense system. In addition, the PHNQs extract, in combination with Antimycin A, displayed a synergistic pro-apoptotic effect, envisaging its possible employment against chemoresistance in cancer treatments. Overall, this study highlights the validity of a zero-waste approach in the seafood chain to obtain high-value products, which, in turn, may be exploited for different biomedical applications.

The approval of anticancer therapeutic strategies is still slowed down by the lack of models able to faithfully reproduce in vivo cancer physiology. On one hand, the conventional in vitro models fail to recapitulate the organ and tissue structures, the fluid flows, and the mechanical stimuli characterizing the human body compartments. On the other hand, in vivo animal models cannot reproduce the typical human tumor microenvironment, essential to study cancer behavior and progression. This study reviews the cancer-on-chips as one of the most promising tools to model and investigate the tumor microenvironment and metastasis. We also described how cancer-on-chip devices have been developed and implemented to study the most common primary cancers and their metastatic sites. Pros and cons of this technology are then discussed highlighting the future challenges to close the gap between the pre-clinical and clinical studies and accelerate the approval of new anticancer therapies in humans., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Determining the potential cardiotoxicity and pro-arrhythmic effects of drug candidates remains one of the most relevant issues in the drug development pipeline (DDP). New methods enabling to perform more representative preclinical in vitro studies by exploiting induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are under investigation to increase the translational power of the outcomes. Here we present a pharmacological campaign conducted to evaluate the drug-induced QT alterations and arrhythmic events on uHeart, a 3D miniaturized in vitro model of human myocardium encompassing iPSC-CM and dermal fibroblasts embedded in fibrin. uHeart was mechanically trained resulting in synchronously beating cardiac microtissues in 1 week, characterized by a clear field potential (FP) signal that was recorded by means of an integrated electrical system. A drug screening protocol compliant with the new International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines was established and uHeart was employed for testing the effect of 11 compounds acting on single or multiple cardiac ion channels and well-known to elicit QT prolongation or arrhythmic events in clinics. The alterations of uHeart's electrophysiological parameters such as the beating period, the FP duration, the FP amplitude, and the detection of arrhythmic events prior and after drug administration at incremental doses were effectively analyzed through a custom-developed algorithm. Results demonstrated the ability of uHeart to successfully anticipate clinical outcome and to predict the QT prolongation with a sensitivity of 83.3%, a specificity of 100% and an accuracy of 91.6%. Cardiotoxic concentrations of drugs were notably detected in the range of the clinical highest blood drug concentration (Cmax), qualifying uHeart as a fit-to-purpose preclinical tool for cardiotoxicity studies., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology.)

For improving the management of the production chain of PGI Mantua pears (which comprises many varieties, including Abate Fetel), applying the cardinal principles of circular economy and sustainability, the fruits with diseases or defects were recovered for producing dried rounds of pears from the Abate Fetel cultivar, a new product with high nutritional value that extends the remaining life. This process led to the production of secondary and residual by-products, which are mainly composed of the highest and lowest part of the fruits, comprising seeds, pulps, peels and petioles. Hence, this study was focused on the valorization of these secondary by-products of Abate Fetel pears through the production of pear extracts using traditional and "green" extraction methods that involve the use of supercritical CO 2 fluid extraction. The produced extracts, together with a reference solvent-derived extract, were analyzed by HPLC-ESI-MS, and in parallel, their direct and cellular antioxidant activity were assessed. Evidence has indicated that all the tested extracts reduced the H 2 O 2 -induced reactive oxygen species (ROS), lipid peroxidation and nitric oxide (NO) levels, respectively, in human intestinal Caco-2 cells. Hence, this study clearly suggests that extracts obtained from Mantuan PGI pear by-products may be used as valuable sources of bioactive upcycled phytocomplex for the development of dietary supplements and/or functional foods.

The research for alternative administration methods for anticancer drugs, towards enhanced effectiveness and selectivity, represents a major challenge for the scientific community. In the last decade, polymeric nanostructured delivery systems represented a promising alternative to conventional drug administration since they ensure secure transport to the selected target, providing active compounds protection against elimination, while minimizing drug toxicity to non-target cells. In the present research, poly(glycerol sebacate), a biocompatible polymer, was synthesized and then nanostructured to allow curcumin encapsulation, a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of Curcuma longa L. Curcumin was selected as an anticancer agent in virtue of its strong chemotherapeutic activity against different cancer types combined with good cytocompatibility within healthy cells. Despite its strong and fascinating biological activity, its possible exploitation as a novel chemotherapeutic has been hampered by its low water solubility, which results in poor absorption and low bioavailability upon oral administration. Hence, its encapsulation within nanoparticles may overcome such issues. Nanoparticles obtained through nanoprecipitation, an easy and scalable technique, were characterized in terms of size and stability over time using dynamic light scattering and transmission electron microscopy, confirming their nanosized dimensions and spherical shape. Finally, biological investigation demonstrated an enhanced cytotoxic effect of curcumin-loaded PGS-NPs on human cervical cancer cells compared to free curcumin.

The valorization of biomass residuals constitutes a key aspect of circular economy and thus a major challenge for the scientific community. Among industrial wastes, plant residuals could represent an attractive source of bioactive compounds. In this context, a residue from the industrial extraction of Cucurbita pepo L. seeds, whose oil is commercialized for the treatment of genito-urinary tract pathologies, has been selected. Supercritical CO 2 technology has been employed as a highly selective "green" methodology allowing the recovery of compounds without chemical degradation and limited operational costs. Free fatty acids have been collected in mild conditions while an enrichment in sterols has been selectively obtained from sc-CO 2 extracts by appropriate modulation of process parameters (supercritical fluid pressure and temperature), hence demonstrating the feasibility of the technique to target added-value compounds in a selective way. Obtained fatty acids were thus converted into the corresponding ethanol carboxamide derivatives by lipase-mediated biocatalyzed reactions, while the hydroxylated derivatives of unsaturated fatty acids were obtained by stereoselective hydration reaction under reductive conditions in the presence of a selected FADH 2 -dependent oleate hydratase., Competing Interests: The authors declare no conflict of interest.

Landfills still represent the main option for waste disposal in many parts of the world. Anyway, they often pose a significant pollution risk and contribute to potential environmental and human health impacts via gaseous and liquid (leachate) emission pathways if not properly managed. Some innovative technologies can help to reduce these emissions, such as in situ aeration and the application of microbial electrochemical technologies (METs). METs are an emerging field that open the possibility to control microbial reactions, enhancing electron flows from electron donors towards electron acceptors. To this end, several materials with different electrochemically-active properties are used, such as electrical conductivity, capacitance, surface electroactivity and charge. The present project named LA-LA-LAND ( La ndfill electron- La pping for a LAND scape requalification) was aimed to apply METs to treat leachate-saturated zones in old landfills. A MET prototype was constructed using a granular anode (graphite) and a cylindrical air-cathode (electroactive biochar). The METs were integrated to three identical laboratory-scale landfill bioreactors coupled with the in situ aeration technique, while three control reactors run without MET. The maximum values of current and power density obtained were 0.015 A·m -2 and 0.00035 W·m -2 . The influence of the MET system on the organic matter removal was evident in two reactors, where this technology was applied, with respect to the control ones: total organic carbon decreased on average 13%, while it reduced less than 5% in the control reactors. This preliminary experiment pointed out some critical aspects of MET configuration, such as the weakness of the cathode architecture, which was prone to be flooded by leachate, blocking the aeration flux.

Commonly known as "purple sea urchin," Paracentrotus lividus occurs in the Mediterranean Sea and the eastern Atlantic Ocean. This species is a highly appreciated food resource and Italy is the main consumer among the European countries. Gonads are the edible part of the animal but they represent only a small fraction (10-30%) of the entire sea urchin mass, therefore, the majority ends up as waste. Recently, an innovative methodology was successfully developed to obtain high-value collagen from sea urchin by-products to be used for tissue engineering. However, tissues used for the collagen extraction are still a small portion of the sea urchin waste (<20%) and the remaining part, mainly the carbonate-rich test and spines, are discarded. Residual cell tissues, tests, and spines contain polyunsaturated fatty acids, carotenoids, and a class of small polyphenols, called polyhydroxynaphthoquinones (PHNQ). PHNQ, due to their polyhydroxylated quinonoid nature, show remarkable pharmacologic effects, and have high economic significance and widespread application in several cosmetic and pharmaceuticals applications. A green extraction strategy aimed to obtain compounds of interest from the wastes of sea urchins was developed. The core strategy was the supercritical CO 2 technique, characterized by low environmental impacts. Fatty acids and carotenoids were successfully and selectively extracted and identified depending on the physical parameters of the supercritical CO 2 extraction. Finally, the exhausted powder was extracted by solvent-based procedures to yield PHNQ. The presence of Spinochrome A and Spinochrome B was confirmed and extracts were characterized by a remarkably high antioxidant activity, measured through the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. Overall, the selective and successive extraction methods were validated for the valorization of waste from sea urchins, demonstrating the feasibility of the techniques targeting added-value compounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Marzorati, Martinelli, Sugni and Verotta.)

The liver is one of the most studied organs of the human body owing to its central role in xenobiotic and drug metabolism. In recent decades, extensive research has aimed at developing in vitro liver models able to mimic liver functions to study pathophysiological clues in high-throughput and reproducible environments. Two-dimensional (2D) models have been widely used in screening potential toxic compounds but have failed to accurately reproduce the three-dimensionality (3D) of the liver milieu. To overcome these limitations, improved 3D culture techniques have been developed to recapitulate the hepatic native microenvironment. These models focus on reproducing the liver architecture, representing both parenchymal and nonparenchymal cells, as well as cell interactions. More recently, Liver-on-Chip (LoC) models have been developed with the aim of providing physiological fluid flow and thus achieving essential hepatic functions. Given their unprecedented ability to recapitulate critical features of the liver cellular environments, LoC have been extensively adopted in pathophysiological modelling and currently represent a promising tool for tissue engineering and drug screening applications. In this review, we discuss the evolution of experimental liver models, from the ancient 2D hepatocyte models, widely used for liver toxicity screening, to 3D and LoC culture strategies adopted for mirroring a more physiological microenvironment for the study of liver diseases., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A red pigment was prepared by reaction of chlorogenic acid (CGA) with tryptophan (TRP) in air at pH 9 (37% w/w yield) and evaluated as food dye. The main component of pigment was formulated as an unusual benzochromeno[2,3-b]indole linked to a TRP unit, featuring a cyanine type chromophore (λ max 542, 546 nm, 1% extinction coefficient of the sodium salt = 244 ± 2). The chromophore showed a minimal pH dependence and proved stable for at least 3 h at 90 °C, both at pH 3.6 or 7.0, whereas red wine anthocyanins showed a substantial (30%) and betanin a complete abatement after 1 h at the acidic pHs. An intense coloring of different food matrices was obtained with the pigment at 0.01 % w/w. No toxicity was observed up to 0.2 mg/mL on hepatic and colonic cell lines. These data make this dye a promising alternative for red coloring of food., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A microfluidic technique is presented for micropatterning protein domains and cell cultures within permanently bonded organs-on-chip devices. This method is based on the use of polydimethylsiloxane layers coupled with the plasma ablation technique for selective protein removal. We show how this technique can be employed to generate a multi-organ in vitro model directly within a microscale platform suitable for pharmacokinetic-based drug screening. We miniaturized a liver model based on micropatterned co-cultures in dual-compartment microfluidic devices. The cytotoxic effect of liver-metabolized Tegafur on colon cancer cell line was assessed using two microfluidic devices where microgrooves and valves systems are used to model drug diffusion between culture compartments. The platforms can reproduce the metabolism of Tegafur in the liver, thus killing colon cancer cells. The proposed plasma-enhanced microfluidic protein patterning method thus successfully combines the ability to generate precise cell micropatterning with the intrinsic advantages of microfluidics in cell biology., (© 2021 IOP Publishing Ltd.)

Cardiac toxicity still represents a common adverse outcome causing drug attrition and post-marketing withdrawal. The development of relevant in vitro models resembling the human heart recently opened the path towards a more accurate detection of drug-induced human cardiac toxicity early in the drug development process. Organs-on-chip have been proposed as promising tools to recapitulate in vitro the key aspects of the in vivo cardiac physiology and to provide a means to directly analyze functional readouts. In this scenario, a new device capable of continuous monitoring of electrophysiological signals from functional in vitro human hearts-on-chip is here presented. The development of cardiac microtissues was achieved through a recently published method to control the mechanical environment, while the introduction of a technology consisting in micro-electrode coaxial guides allowed to conduct direct and non-destructive electrophysiology studies. The generated human cardiac microtissues exhibited synchronous spontaneous beating, as demonstrated by multi-point and continuous acquisition of cardiac field potential, and expression of relevant genes encoding for cardiac ion-channels. A proof-of-concept pharmacological validation on three drugs proved the proposed model to potentially be a powerful tool to evaluate functional cardiac toxicity., (Creative Commons Attribution license.)

Among bioactive phytochemicals, ellagic acid (EA) is one of the most controversial because its high antioxidant and cancer-preventing effects are strongly inhibited by low gastrointestinal absorption and rapid excretion. Strategies toward an increase of solubility in water and bioavailability, while preserving its structural integrity and warranting its controlled release at the physiological targets, are therefore largely pursued. In this work, EA lysine salt at 1:4 molar ratio (EALYS), exhibiting a more than 400 times increase of water solubility with respect to literature reports, was incorporated at 10% in low methoxylated (LM) and high methoxylated (HM) pectin films. The release of EA in PBS at pH 7.4 from both film preparations was comparable and reached 15% of the loaded compound over 2 h. Under simulated gastric conditions, release of EA from HM and LM pectin films was minimal at gastric pH, whereas higher concentrations-up to 300 μM, corresponding to ca. 50% of the overall content-were obtained in the case of the HM pectin film after 2 h incubation at the slightly alkaline pH of small intestine environment, with the enzyme and bile salt components enhancing the release. EALYS pectin films showed a good prebiotic activity as evaluated by determination of short chain fatty acids (SCFAs) levels following microbial fermentation, with a low but significant increase of the effects produced by the pectins themselves. Overall, these results highlight pectin films loaded with EALYS salt as a promising formulation to improve administration and controlled release of the compound.

Phenolic compounds are broadly represented in plant kingdom, and their occurrence in easily accessible low-cost sources like wastes from agri-food processing have led in the last decade to an increase of interest in their recovery and further exploitation. Indeed, most of these compounds are endowed with beneficial properties to human health (e.g., in the prevention of cancer and cardiovascular diseases), that may be largely ascribed to their potent antioxidant and scavenging activity against reactive oxygen species generated in settings of oxidative stress and responsible for the onset of several inflammatory and degenerative diseases. Apart from their use as food supplements or as additives in functional foods, natural phenolic compounds have become increasingly attractive also from a technological point of view, due to their possible exploitation in materials science. Several extraction methodologies have been reported for the recovery of phenolic compounds from agri-food wastes mostly based on the use of organic solvents such as methanol, ethanol, or acetone. However, there is an increasing need for green and sustainable approaches leading to phenolic-rich extracts with low environmental impact. This review addresses the most promising and innovative methodologies for the recovery of functional phenolic compounds from waste materials that have appeared in the recent literature. In particular, extraction procedures based on the use of green technologies (supercritical fluid, microwaves, ultrasounds) as well as of green solvents such as deep eutectic solvents (DES) are surveyed., (Copyright © 2020 Panzella, Moccia, Nasti, Marzorati, Verotta and Napolitano.)